Release of sulfur mustard-modified DNA bases by Escherichia coli 3-methyladenine DNA glycosylase II

The toxic effects of sulfur mustard have been attributed toDNA modification with the formation of 7-hydroxyethyl-thioethylguanine, 3-hydroxyethylthioethyl adenine and the cross-link,di-(2-guanin-7-yl-ethyl)sulfide. To investigate the action ofbacterial 3-methyladenine DNA glycosylase II (Gly II) on theseadducts, calf thymus DNA was modified with [¹⁴C]sulfur mustardand used as a substrate for Gly II. Gly II releases both 3-hydroxyethylthioethyladenine and 7-hydroxyethylthioethyl guanine from this substrate.In comparison with the activity of Gly II towards methylatedDNA, 3-hydroxyethylthioethyl adenine is released somewhat moreslowly than 3-methyladenine, while 7-hydroxyethylthioethyl guanineis released much more readily than 7-methylguanine. Glycosylaseaction may play a role in protecting cells from the toxic effectsof sulfur mustard.